The present invention relates to systems for tissue characterization based on impedance measurements, and in particular to systems for skin cancer characterization.
Skin cancer, such as melanoma, Basal cell carcinoma (BCC), Squamous cell carcinoma (SCC), is a type of cancer which afflicts many people. Early detection of skin cancer dramatically increases the probability of successful removal of the skin cancer. Conventional methods of skin cancer detection include visual inspection of suspected skin moles for characteristics of malignant tumors. These characteristics include asymmetry (i.e., one half of the mole does not match the other half), border irregularity (i.e., the edges are of the mole are ragged, notched or blurred), color (i.e., the pigmentation of the mole is not uniform) and diameter (i.e., the mole has a diameter greater than 6 millimeters) and are referred to together as the ABCD test. When a mole is identified as suspicious, a biopsy sample is taken for a more definite analysis. The percentage of positive cancer indications in melanoma biopsy tests is currently very low, i.e., less than 1%. In order to reduce the number of unnecessary biopsies, and to increase the rates of early identification of melanoma, a non-invasive method for identification of skin cancer, more objective and accurate than the ABCD test, is required.
In some cases, cameras are used to capture images of suspicious skin lesions, to allow follow up of the lesion. Images of a lesion are taken from different distances, chosen as a compromise between the accuracy achieved from being very close to the skin and the capturing a wide view of the surroundings by being very far from the skin. There exists, for example, a system which includes a pair of cameras for imaging skin lesions. A first camera is used for close-up images, and a second camera is used for various other distances farther from the skin.
Variations in electrical impedance have been suggested for use in detection of anomalies and various types of cancer, particularly breast cancer. For example, U.S. Pat. Nos. 4,291,708, 4,458,694, and 5,810,742 and the article, xe2x80x9cBreast Cancer Screening by Impedance Measurements,xe2x80x9d by G. Piperno et al., Frontiers Med. Biol. Eng., Vol. 2 pp. 111-117, the disclosures of which are incorporated herein by reference, describe systems for determining the impedance between a point on the surface of the skin and some reference point on the body of the patient. With the use of a multi-element probe, a two-dimensional impedance map of an organ such as a breast can be generated. The impedance map, describing variations in impedance along the tissue of the organ, can be used for the detection of tumors and especially malignant tumors.
U.S. Pat. No. 4,291,708 to Frei, mentioned above, describes a probe for placement on a surface being imaged. A plurality of generally flat sensing elements are mounted on the probe in a generally planar arrangement or in a configuration fitting to the human breast.
UK patent application GB 2 276 326, filed Mar. 22, 1994, the disclosure of which is incorporated herein by reference, describes a bio-signal electrode which has a rough surface in order to improve the contact with the skin. Points of the rough surface penetrate the epidermal layer of the skin.
UK patent application GB 2 138 148, filed Apr. 13, 1984, the disclosure of which is incorporated herein by reference, describes mounting of electrodes on respective pneumatic or hydraulic cylinders which keep the electrodes at a common pressure level relative to the skin.
U.S. Pat. No. 5,353,802 to Ollmar, the disclosure of which is incorporated herein by reference, describes a device for depth selective measurement of impedance in the human body. The device is suggested for detection and characterization of surface phenomena in organic and biological material.
U.S. Pat. No. 6,026,323 to Skadlev, the disclosure of which is incorporated herein by reference, describes an instrument for detection of cervical cancer and other surface cancers. The instrument combines optical and electrical devices, which perform complex tests on the cervix of a patient and on other surfaces of a patient such as the skin. The instrument of the U.S. Pat. No. 6,026,323 patent includes three electrodes, which are used to sense the local impedance at the point of contact of the electrodes.
An aspect of some embodiments of the present invention relates to an electrode head that holds one or more bio-compatible electrodes for in vivo impedance imaging. The electrode head comprises a rigid electrode head formed of one or more PCBs (printed circuit boards) on which the electrodes are mounted. In some embodiments of the invention, the rigid electrode head is formed of one or more rigid PCBs. Alternatively, the electrode head is formed of a plurality of PCBs, at least one of which is a flexible PCB, which are stiffened by their attachment. Generally, a rigid electrode head does not conform to the shape of a surface against which it is pressed. The use of a rigid electrode head ensures that the relative orientation of electrodes mounted on the electrode head is known and/or planar. Therefore, generation of an image from signals sensed by the electrodes is simpler relative to use of flexible PCBs. Also, a rigid electrode head serves as a more solid base for electrodes adapted to penetrate a tissue surface of a patient, as described hereinbelow for some embodiments of the invention.
In some embodiments of the invention, the one or more electrodes are mounted on one or more edges of the one or more PCBs. Optionally, the electrode head comprises a plurality of PCBs which are attached with their surface areas (i.e., faces) facing each other.
An aspect of some embodiments of the present invention relates to an electrode head including one or more electrodes protruding from one or more edges of the one or more PCBs. In some embodiments of the invention, the one or more electrodes comprise ends of conductive wires running along one or more of the PCBs. In some embodiments of the invention, the electrodes have an axis parallel to the surface of the PCB, such that the electrode contacts the skin of a patient axially. Optionally, the electrodes extend beyond the edge of the PCB. In some embodiments of the invention, the electrodes comprise sharp points, which penetrate the stratum corneum of the skin surface, without penetrating the epidermal layer. Optionally, the sharp points penetrate to a depth of between about 30-50 xcexcm.
An aspect of some embodiments of the present invention relates to an electrode head that includes a plurality of PCBs permanently combined. Optionally, the PCBs are combined along their faces. In some embodiments of the invention, each of the PCBs is connected to at least one neighboring PCB such that at least part of the face area of the PCB covers most of the face area of the neighboring PCB.
An aspect of some embodiments of the present invention relates to a bio-medical probe including one or more sensing elements. The probe does not allow sensing of electrical signals, unless a physician presses the probe against the tissue surface with at least a minimal predetermined force. Optionally, not allowing the sensing of the electrical signals comprises not applying a stimulus signal required for sensing the signals. Alternatively or additionally, not allowing the sensing of the electrical signals comprises disconnecting a sensing circuit from the one or more sensing elements and/or marking acquired signals as invalid. Further alternatively or additionally, not allowing the sensing of the electrical signals comprises preventing contact between the sensing elements and an inspected tissue surface. In some embodiments of the invention, the probe includes a stopper which constrains the advancement of the sensing elements toward the tissue surface unless the minimal force is applied. The stopper is optionally mounted on a pressure exerting device, e.g., springs, pneumatic devices, hydraulic devices, relative to the electrodes, such that the electrodes do not contact the tissue surface, unless the probe is pressed against the surface with at least the minimal predetermined force. The minimal predetermined force is optionally selected such that the coupling between the electrodes and the tissue surface is substantially constant for pressure levels above the predetermined force. In exemplary embodiments of the invention, the minimal force comprises between about 0.25-1 kg/force, optionally about 0.5 kg/force. Thus, the coupling between the electrodes and the surface of the patient does not substantially depend on the force exerted by a physician pressing the probe against the surface of the patient.
In some embodiments of the invention, the stopper and the sensing elements are mounted on the probe in a manner that allows constrained movement relative to each other. In some embodiments of the invention, the mounting of the stopper and the electrodes allows constrained movement in only one direction, optionally in the axial direction. Optionally, the stopper surrounds the one or more sensing electrodes. In some embodiments of the invention, the stopper comprises a guard ring which keeps the tissue surrounding the sensing electrodes at an equipotential (e.g., grounded). Alternatively, the stopper is held at a different, optionally lower, potential than the potential at which tips 108 are held. In some embodiments of the invention, the electrodes are allowed to advance up to a predetermined distance (e.g., 0.5-3 mm) beyond the stopper.
An aspect of some embodiments of the present invention relates to a dual modality hand-held probe which includes an array of sensing elements for impedance imaging of a surface of a patient and a camera for acquiring visual images of the surface. In some embodiments of the invention, the hand-held probe is associated with a processor that registers the impedance images with the visual images. Alternatively or additionally, the processor analyzes the impedance images and/or visual images to provide an indication on the probability of a malignant tumor on the surface. The processor may be included within the probe or may be in communication with the probe.
An aspect of some embodiments of the present invention relates to a bio-medical probe which includes one or more electrodes with sharp points, adapted to penetrate the stratum corneum of the skin of a patient, without penetrating the epidermal layer of the skin. In an exemplary embodiment of the invention, the sharp points of the electrodes are allowed to penetrate to a depth of up to 30-50 xcexcm.
An aspect of some embodiments of the present invention relates to using a probe with sharp points in an impedance imaging procedure for skin examination and/or analysis.
An aspect of some embodiments of the present invention relates to a skin examination and/or analysis procedure, e.g., a cancer screening procedure, in which a two-dimensional array of sensing elements is used to generate an impedance image of a skin region, for example, of a suspected anomaly on the skin. In accordance with this aspect of the present invention, a skin image is generated responsive to the measurements from the sensing elements, rather than a depth image as is performed in the above described art. Using an impedance map allows identifying properties of specific regions within the anomaly.
In some embodiments of the invention, the generated image comprises an image parallel to the array of sensing elements. Optionally, the sensing elements sense currents and each pixel in the impedance image corresponds to measurements from a single sensing element.
An aspect of some embodiments of the present invention relates to a bio-compatible electrode which includes an array of sensing elements in which the distance between adjacent elements is smaller than a millimeter. Optionally, the array comprises a two dimensional array of sensing elements. In some embodiments of the invention, the distance between adjacent sensing elements is smaller than 0.7, 0.6 or even 0.5 millimeters.
An aspect of some embodiments of the invention relates to a camera for acquiring skin images. The camera includes a few distinct focusing states for a single camera casing, but does not include complex zoom apparatus. Thus, the camera includes inexpensive apparatus, which allows acquiring skin images from a few different distances.
In some embodiments of the invention, the few distinct states include between two to four states. In an exemplary embodiment of the invention, the distinct states include a close state in which the camera is placed directly on the skin, and a remote state in which the images are acquired from a predetermined remote distance, e.g., 50, 80 or 100 centimeters.
There is therefore provided in accordance with an embodiment of the invention, an electrode head including at least one bio-compatible electrode, comprising at least one printed circuit board (PCB) having a face area and a thickness and at least one bio-compatible electrode extending from the thickness of the at least one printed circuit board.
Optionally, the at least one printed circuit board comprises a plurality of printed circuit boards attached along their face areas. Optionally, the plurality of printed circuit boards are attached with an adhesive which has at least 70% alcohol resistance.
Optionally, the at least one electrode comprises at least one electrode extending from each of the plurality of printed circuit boards (PCBs). In some embodiments of the invention, the at least one electrode extending from each of the plurality of PCBs comprises at least eight electrodes extending from each of the PCBs. Possibly, the at least one electrode comprises a plurality of electrodes which are held by the electrode head at fixed relative positions.
Optionally, the electrode head includes at least one leading wire running along the at least one PCB and wherein the leading wire is formed as a single piece with one of the electrodes. Optionally, the at least one electrode comprises at least one electrode tapered toward an end of the electrode, distal from the PCB.
There is further provided in accordance with an embodiment of the invention, an electrode head including at least one bio-compatible electrode, comprising a plurality of printed circuit boards (PCBs), and a plurality of electrodes extending from the printed circuit boards, the electrodes being held by the circuit boards at fixed relative positions.
Optionally, the plurality of electrodes comprise gold plated electrodes.
There is further provided in accordance with an embodiment of the invention, an electrode head including at least one bio-compatible electrode, comprising a plurality of printed circuit boards (PCB), each having a face area and a thickness, each of the PCBs being positioned with respect to at least one other PCB such that at least a portion of its face area overlaps most of the face area of the other PCB; and at least one bio-compatible electrode extending from at least one of the printed circuit boards.
Optionally, each of the PCBs is connected to at least one other PCB such that substantially all of its face area overlaps substantially all of the face area of the other PCB.
There is further provided in accordance with an embodiment of the invention, a bio-medical probe, comprising at least one electrode for placement on a tissue surface, a sensing circuit adapted to acquire signals impinging on the at least one electrode, wherein the sensing circuit is adapted to acquire the signals only if the at least one electrode is pressed against the tissue surface with at least a predetermined force.
Optionally, the at least one electrode comprises a two-dimensional array of electrodes. Optionally, the electrodes of the two-dimensional array are located on a single flat plane and/or are organized in a rectangular array. Optionally, the at least one electrode comprises one or more electrodes with pointed tips adapted to penetrate the tissue surface.
Optionally, the sensing circuit is adapted to provide a user indication when the at least one electrode is pressed against the tissue surface with at least the predetermined force. Optionally, the sensing circuit is prevented from acquiring signals when the at least one electrode is pressed against the tissue surface with at least the predetermined force.
Optionally, the sensing circuit marks signals acquired when the at least one electrode is not pressed against the tissue surface with at least the predetermined force, as invalid. Optionally, the at least one electrode does not contact the tissue surface unless the at least one electrode is pressed against the tissue surface with at least the predetermined force. Optionally, the probe includes a stopper which prevents the at least one electrode from contacting the tissue surface unless the at least one electrode is pressed against the tissue surface with at least the predetermined force.
Optionally, the probe includes a power source for applying an equipotential to the stopper. Optionally, the probe includes at least one pressure exerting device which pushes the stopper toward the tissue surface. Optionally, the at least one pressure exerting device comprises at least one spring, pneumatic device and/or hydraulic device. Optionally, the probe includes a light source adapted to illuminate a tissue surface around which the stopper is placed. Optionally, the probe includes the predetermined force comprises between about 0.25 to 1 kilogram/force.
There is further provided in accordance with an embodiment of the invention, a bio-medical probe, comprising at least one electrode for placement on a tissue surface; and a stopper coupled to the at least one electrode in a manner which allows relative movement of the stopper relative to the at least one electrode, and prevents the at least one electrode from passing the stopper by more than a predetermined distance.
Optionally, the at least one electrode is adapted to contact the tissue surface only when the stopper is pressed against the tissue surface by at least a predetermined force. Optionally, the probe includes a power source adapted to apply an equipotential to the stopper. Optionally, the stopper is coupled to the at least one electrode through at least one pressure exerting device. Optionally, the pressure exerting device comprises a spring. Optionally, the at least one electrode is surrounded by the stopper.
There is further provided in accordance with an embodiment of the invention, a method of impedance imaging, comprising pressing at least one electrode against a tissue surface, such that the at least one electrode penetrates the tissue surface without penetrating the epidermis and sensing electrical signals from the at least one electrode.
Optionally, the at least one electrode penetrates the tissue surface by at least 20 xcexcm or 70 xcexcm. Optionally, pressing the at least one electrode against the tissue surface comprises pressing the at least one electrode against a tissue surface on which a lesion was identified. Optionally, the at least one electrode comprises a two-dimensional array of electrodes. Optionally, the method includes displaying an impedance image responsive to the signals sensed by the array of electrodes. Optionally, the at least one electrode is pointed at its distal end.
There is further provided in accordance with an embodiment of the invention, a method of examining a tissue surface of a patient, comprising placing a probe including at least one sensing element on a tissue surface, such that the at least one sensing element penetrates the tissue surface, sensing electrical signals by the at least one sensing element; and providing an indication on the tissue surface responsive to the sensed signals.
Optionally, providing the indication on the tissue surface comprises providing an impedance map of the tissue surface and/or an indication on a probability that the tissue surface includes a cancerous tumor. Optionally, the method includes identifying a suspected tissue surface anomaly and placing the probe on the tissue surface comprises placing the probe above the suspected anomaly. Optionally, placing the probe on the tissue surface comprises placing a probe which includes a plurality of sensing elements on the tissue surface. Optionally, placing the probe on the tissue surface comprises placing a probe which includes a two-dimensional array of sensing elements on the tissue surface.
Optionally, the method includes applying a stimulus signal to the patient remote from the tissue surface on which the probe is placed and wherein sensing the electrical signals comprises sensing electrical signals generated responsive to the applied stimulus signal. Optionally, the at least one sensing element penetrates the tissue surface by less than 70 xcexcm. Optionally, the tissue surface comprises a skin surface, a cervix and/or rectum of the patient. Optionally, the at least one sensing element taper off with a sharp point.
There is further provided in accordance with an embodiment of the invention, a method of examining a tissue surface of a patient, comprising placing a probe including at least one sensing element on a tissue surface, the at least one sensing element is tapered toward the tissue surface, sensing electrical signals by the at least one sensing element; and providing an indication on the tissue surface responsive to the sensed signals.
Optionally, the sensing elements have a triangular shape pointed toward the tissue surface. Alternatively or additionally, the sensing elements have a concave shape facing the tissue surface. Further alternatively or additionally, the sensing elements have a convex shape facing the tissue surface. Optionally, the method includes identifying a suspected tissue surface anomaly and placing the probe on the tissue surface comprises placing the probe above the suspected anomaly.
There is further provided in accordance with an embodiment of the invention, a method of examining a skin surface of a patient, comprising identifying a suspected skin lesion, placing a probe including a plurality of sensing elements on a skin surface above the identified lesion, sensing electrical signals by the plurality of sensing elements; and generating an impedance map responsive to the sensed signals.
Optionally, identifying the suspected lesion comprises visually identifying the lesion. Optionally, the plurality of sensing elements are included in a planar array of elements and wherein generating the impedance map comprises generating a map parallel to the planar array. Optionally, generating the map comprises generating a map in which each pixel corresponds to a respective sensing element of the plurality of sensing elements. Optionally, generating the impedance map comprises generating a map including at least 32, 64, 128 or 256 pixels. Optionally, the method includes acquiring at least one impedance map of an area adjacent the skin lesion but not including the skin lesion. Optionally, the method includes providing a malignancy level indication responsive to the sensed electrical signals and the at least one impedance map of an area adjacent the skin lesion.
Optionally, generating the impedance map responsive to the sensed signals is performed using at least one parameter selected responsive to the at least one impedance map of an area adjacent the skin lesion. Possibly, generating the impedance map responsive to the sensed signals comprises dividing the value of each pixel by a respective value of the at least one impedance map of an area adjacent the skin lesion. Optionally, acquiring the at least one impedance map comprises acquiring at least two impedance maps on opposite sides of the lesion. Optionally, the method includes acquiring at least one optical image of the lesion. Optionally, acquiring the at least one optical image of the lesion comprises acquiring at least one close-up image and at least one far shot image.
There is further provided in accordance with an embodiment of the invention, an electrode head including an array of bio-compatible sensing elements, comprising a substrate, and a plurality of sensing elements mounted on the substrate such that the distance between each two neighboring sensing elements is smaller than 1 mm. Optionally, the plurality of sensing elements are organized in a rectangular array. Optionally, the distance between each two neighboring sensing elements is smaller than 0.5 mm.
There is further provided in accordance with an embodiment of the invention, a probe for skin cancer examination, comprising a hand held casing, an impedance probe, adapted to sense electrical signals from a tissue surface, encased in the hand held casing, and a camera, adapted to acquire images of the tissue surface, encased in the hand held casing.
Optionally, the camera has a predetermined number of distinct focusing states.
There is further provided in accordance with an embodiment of the invention, a camera for acquiring images of skin lesions, comprising an image acquiring unit adapted to acquire images of tissue surface lesions, and a lens adapted to be positioned in a plurality of distinct focusing positions, which determine the focus distance of an image from the lens.
Optionally, the lens has only two distinct focusing positions. Optionally, one focusing position is adapted for acquiring images when the camera is placed on the tissue surface. Alternatively or additionally, one focusing position is adapted for acquiring images when the camera is distanced from the tissue surface by at least 50 cm.
Optionally, the camera does not include zoom apparatus.
There is further provided in accordance with an embodiment of the invention, a method of examining a patient, comprising identifying a suspected lesion, acquiring at least one first impedance measurement of an area surrounding the suspected lesion but not including the suspected lesion, acquiring at least one second impedance measurement including at least a portion of the lesion, and providing an indication on the lesion responsive to the at least one second impedance measurement, wherein acquiring the at least one second impedance measurement or providing the indication is performed using at least one parameter having a value determined responsive to the at least one first impedance measurement.
Optionally, identifying the lesion comprises identifying a tissue surface lesion.
In some embodiments of the invention, identifying the tissue surface lesion comprises identifying a cervix or skin lesion. Optionally, acquiring the at least one first impedance measurement comprises acquiring an impedance image comprising a plurality of pixels. Optionally, acquiring the at least one second impedance measurement comprises acquiring an impedance image of the lesion which includes a plurality of pixels.
Optionally, providing the indication comprises displaying the impedance image of the lesion. Optionally, the at least one parameter comprises a normalization parameter. Optionally, the at least one normalization parameter comprises a normalization map which includes for each pixel of the impedance image a respective normalization value.
There is further provided in accordance with an embodiment of the invention, a method of providing an indication on a malignancy level of an anomaly, comprising generating a multi-pixel impedance image of the anomaly, each pixel having a value of an image impedance related parameter, selecting a sub-group of pixels of the impedance image, including fewer pixels than included in the image, at least partially based on information external to the impedance image, and providing an indication on the malignancy level of the anomaly responsive to the value of the image impedance related parameter of the selected sub-group of pixels.
Optionally, generating the impedance image of the anomaly comprises generating an impedance image of a skin anomaly. Possibly, selecting the sub-group of pixels comprises selecting solely responsive to information external to the impedance image.
Optionally, selecting the sub-group of pixels comprises selecting responsive to an additional impedance image in which each pixel has a value of an additional impedance related parameter. Optionally, the impedance related parameter comprises a conductance measured at a specific image frequency. Optionally, the additional impedance related parameter comprises a conductance measured at a second frequency different from the specific image frequency. Possibly, selecting the sub-group of pixels comprises selecting responsive to an optical image of the anomaly. Optionally, selecting the sub-group of pixels comprises selecting a predetermined number of pixels and/or selecting pixels at positions which fulfill a predetermined requirement.